In laboratory studies using mice, researchers from the University of Adelaide in South Australia have been able to switch off the impulse to drink alcohol by giving mice a drug that blocks the immune system in the brain.

Now published in the journal Brain, Behavior and Immunity, this research is one of the first of its kind to show a link between the brain’s immunity and the motivation to drink alcohol, particularly in the evening.

“Alcohol is the world’s most commonly consumed drug, and there is a greater need than ever to understand the biological mechanisms that drive our need to drink alcohol,” said lead author Jon Jacobsen, PhD student in the University of Adelaide’s Discipline of Pharmacology.

“Our body’s circadian rhythms affect the ‘reward’ signals we receive in the brain from drug-related behaviour, and the peak time for this reward typically occurs during the evening, or dark phase. We wanted to test what the role of the brain’s immune system might have on that reward, and whether or not we could switch it off.”

Jacobsen said the drug, (+)-Naltrexone, also had interesting affects on adolescent mice.

“If you give this drug to adolescent mice after they’ve consumed alcohol you block these negative affects associated with alcohol use later on in life,” he said.

“We know that adolescents that engage in this binge drinking behavior can have much more profound problems later on in life – they are much more likely to engage in things like alcohol dependence and risky behavior when they are adults.”

The researchers focused their attention on the immune receptor Toll-like receptor 4 (TLR4). They administered the drug (+)-Naltrexone (pronounced: PLUS-NAL-TREX-OWN), which is known to block TLR4, to mice.

The compound used in pre-clinical studies specifically targets the brain’s immune system as opposed to Naltrexone, a drug commonly used to treat alcoholism, which targets brain cells more generally.

“Our studies showed a significant reduction in alcohol drinking behaviour by mice that had been given (+)-Naltrexone, specifically at night time when the reward for drug-related behaviour is usually at its greatest,” Jacobsen said.

“We concluded that blocking a specific part of the brain’s immune system did in fact substantially decrease the motivation of mice to drink alcohol in the evening.”

“What we are really beginning to understand now is that the brain has this complex immune system of its own so giving a drug that blocks the immune system may have these other side effects we don’t yet know,” Jacobsen said.

Senior author Professor Mark Hutchinson, Director of the ARC Centre of Excellence for Nanoscale BioPhotonics at the University of Adelaide and leader of the Neuroimmunopharmacology lab in which the work was conducted, said the findings pointed to the need for further research to understand the implications for drinking behaviour in humans.

“Our study is part of an emerging field which highlights the importance of the brain’s immune system in the desire to drink alcohol,” Professor Hutchinson said.

“Given the drinking culture that exists in many nations around the world, including Australia, with associated addiction to alcohol and related health and societal issues, we hope our findings will lead to further studies.”

The research was funded by the Australian Research Council (ARC), the US National Institute on Drug Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism.

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